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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF CERTAIN
    FOOD ADDITIVES



    WHO FOOD ADDITIVES SERIES 16






    Geneva, 23 March - 1 April 1981




         The International Programme on Chemical Safety (IPCS),
    established in 1980, is a joint venture of the United Nations
    Environment Programme (UNEP), the International Labour Organisation
    (ILO), and the World Health Organization (WHO). The overall objectives
    of the IPCS are to establish the scientific basis for assessment of
    the risk to human health and the environment from exposure to
    chemicals, through international peer-review processes, as a
    prerequisite for the assistance in strengthening national capacities
    for the sound management of chemicals.

         The Inter-Organization Programme for the Sound Management of
    Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and
    Agriculture Organization of the United Nations, WHO, the United
    Nations Industrial Development Organization and the Organisation for
    Economic Co-operation and Development (Participating Organizations),
    following recommendations made by the 1992 UN Conference on
    Environment and Development to strengthen cooperation and increase
    coordination of the policies and activities pursued by the
    Participating Organizations, jointly or separately, to achieve the
    sound management of chemicals in relation to human health and the
    environment.

    WHO Food Additives Series, 1981, No. 16

    TOXICOLOGICAL EVALUATION OF CERTAIN FOOD ADDITIVES

    The evaluations contained in this document

    were prepared by the Joint FAO/WHO

    Expert Committee on Food Additives*

    Geneva, 23 March - 1 April 1981

    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    IPCS

              

    *    Twenty-fifth report of the Joint FAO/WHO Expert Committee on Food
         Additives, Geneva, Wld Hlth Org. techn. Rep. Ser., 669, 1981.

    INTRODUCTION

         The monographs contained in this document have been prepared by
    the Joint FAO/WHO Expert Committee on Food Additives which was held in
    Geneva, 23 March - 1 April 1981.

         Any new information and comments on the biological and
    toxicological data should be addressed to: International Programme on
    Chemical Safety (Food), Division of Environmental Health, World Health
    Organization, Avenue Appia, 1211 Geneva 27, Switzerland.

    JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES

    Geneva, 23 March - 1 April 1981

    Members invited by FAO

    Professor I. S. Bhatia, Professor of Chemistry and Biochemistry,
         Punjab Agricultural University, Ludhiana, India

    Dr W. H. B. Denner, Principal Scientific Officer, Food Science
         Division, Ministry of Agriculture, Fisheries and Food, London,
         England

    Dr S. W. Gunner, Acting Chief, Division of Additives and Pesticides,
         Bureau of Chemical Safety, Food Directorate, Health Protection
         Branch, Department of National Health and Welfare, Ottawa, Canada

    Professor K. Kojima, College of Environmental Health, Azabu
         University, Sagamihara, Japan

    Dr W. Kroenert, Head, Food Chemistry Division, Federal Health
         Institute, Berlin (West) (Vice-Chairman)

    Dr P. F. Noordervliet, Manager, Product Development, Gist-Brocades NV,
         Delft, Netherlands

    Professor F. J. Pellerin, Faculty of Pharmacy, University of Paris XI,
         Emile Roux Hospital Centre, Eaubonne, France

    Members invited by WHO

    Dr H. Blumenthal, Director, Division of Toxicology, Bureau of Foods,
         Food and Drug Administration, Washington, D.C., United States of
         America

    Dr B. Briski, Divisional Chief, Laboratory for Food and Food Additives
         Analysis, Department of Nutrition, Institute of Public Health of
         Croatia, Zagreb, Yugoslavia

    Professor F. A. Fairweather, Director, Toxicology Unit, Department of
         Health and Social Security, London, England (Chairman)

    Dr G. Nazario, Food Standards Commission, National Health Council,
         Ministry of Health, Rio de Janeiro, Brazil

    Professor I. Nir, Department of Pharmacology, Hebrew University
         Hadassah Medical School, Jerusalem, Israel

    Professor M. J. Rand, Chairman, Department of Pharmacology, University
         of Melbourne, Victoria, Australia (Rapporteur)

    Observer invited by FAO

    Mr A. Feberwee, Chairman, Codex Committee on Food Additives, c/o
         Ministry of Agriculture and Fisheries, The Hague, Netherlands

    Secretariat

    Dr J. R. P. Cabral, Division of Chemical and Biological
         Carcinogenesis, International Agency for Research on Cancer,
         Lyons, France

    Dr P.S. Elias, Director, International Food Irradiation Programme,
         Federal Research Centre for Nutrition, Karlsruhe, Federal
         Republic of Germany (WHO Temporary Adviser)

    Professor R. Ferrando, National Veterinary School, Alfort, France
         (FAO Temporary Adviser)

    Dr C. L. Galli, Department of Pharmacology and Pharmacognosy,
         University of Milan, Italy (WHO Temporary Adviser)

    Mr R. Haigh, Principal Administrator, Commission of the European
         Communities, Brussels, Belgium (WHO Temporary Adviser)

    Dr V. L. Kossila, Animal Production Officer, Feed Resources, Animal
         Protection and Health Division, FAO, Rome, Italy

    Dr G. D. Kouthon, Nutrition Officer, Food Policy and Nutrition
         Division, FAO, Rome, Italy (Joint Secretary)

    Dr M. Mercier, Manager of the International Programme on Chemical
         Safety, Division of Environmental Health, WHO, Geneva,
         Switzerland

    Dr I. C. Munro, Director-General, Food Directorate, Health Protection
         Branch, Department of National Health and Welfare, Ottawa, Canada 
          (WHO Temporary Adviser)

    Dr N. Rao Maturu, Food Standards Officer, Joint FAO/WHO Food Standards
         Programme, Food Policy and Nutrition Division, FAO, Rome, Italy

    Dr S. I. Shibko, Chief, Contaminants and Natural Toxicants Evaluation
         Branch, Division of Toxicology, Bureau of Foods, Food and Drug
         Administration, Washington, D.C., United States of America
         (WHO Temporary Adviser)

    Dr P. Shubik, Resident Fellow, Green College, Oxford, England
         (WHO Temporary Adviser)

    Professor R. Truhaut, Director, Toxicological Research Centre, René
         Descartes University, Paris, France (WHO Temporary Adviser)

    Professor W. Velle, Department of Physiology, Veterinary College of
         Norway, Oslo, Norway (FAO Temporary Adviser)

    Dr G. Vettorazzi, Toxicologist, International Programme on Chemical
         Safety, Division of Environmental Health, WHO, Geneva
         (Joint Secretary)

    Dr R. Walker, Department of Biochemistry, University of Surrey,
         Guildford, England (WHO Temporary Adviser)

    Dr A. Zaitsev, Head, Laboratory for the Hygienic Examination of Food
         Additives, Institute of Nutrition, Academy of Medical Sciences,
         Moscow, USSR (WHO Temporary Adviser)

    ACCEPTABLE DAILY INTAKE (ADI) AND INFORMATION ON SPECIFICATIONS

                                             ADI for man (mg/kg of
                         Specifications1     body weight) and other
                                             toxicological decisions

    Food colours

    Allura Red                   R               0-7

    Brilliant Black PN           R               0-1

    Brown HT (formerly
    Chocolate Brown HT)          R               0-2.52

    carmines (formerly
    cochineal, carmine
    and carminic acid)           NT              0-2.52

    Fast Green FCF               S               0-12.52

    Ponceau 4R                   R               0-0.1252

    Red 2G                       R               0-0.1

    riboflavin-5'-phosphate      N               0-0.53

    Flavouring agents

    ß-asarone                    O               No ADI allocated

    (+) carvone and (-)
    carvone                      R               0-12

    cinnamaldehyde               R               0-0.72

    cinnamyl anthranilate        O               Not to be used4

    coumarin                     O               No ADI allocated

    estragole                    NT              No ADI allocated

    ethylmethyl ketone           R               No ADI allocated

    ethyl 3-phenylglycidate      R               No ADI allocated

    eugenyl methyl ether         NT              No ADI allocated

    hydrocyanic acid             O               Not to be used5

    ACCEPTABLE DAILY INTAKE (ADI) AND INFORMATION ON SPECIFICATIONS
    (Con't)

                                             ADI for man (mg/kg of
                         Specifications1     body weight) and other
                                             toxicological decisions

    Flavouring agents (Con't)

    magnesium glutamate          N           0-1206

    maltol                       R           0-1

    methyl ß-naphthyl
    ketone                      RT           No ADI allocated

    octanal                      R           0-0.062

    p-propylanisole             NT           No ADI allocated

    safrole and isosafrole       O           No ADI allocated

    thujone and isothujone
    (alpha- and ß-thujone)       O           No ADI allocated

    Sweetening agents

    acesulfame potassium        NT           No ADI allocated

    aspartame                    R           0-4016

    isomaltitol                 NT           0-252

    Thickening agents

    carob (locust) bean gum      S           ADI not specified7

    pectins                      R           ADI not specified7,8

    pectins (amidated)           N           ADI not specified7

    tara gum                    TS           0-12.52

    Extraction solvents

    light petroleum              R           ADI not specified7

    2-nitropropane           withdrawn       Not to be used9

    propan-1-ol (n-propanol)    RT           No ADI allocated

    ACCEPTABLE DAILY INTAKE (ADI) AND INFORMATION ON SPECIFICATIONS
    (Con't)

                                             ADI for man (mg/kg of
                         Specifications1     body weight) and other
                                             toxicological decisions

    Extraction solvents (Con't)

    propan-2-ol (isopropanol)   RT           No ADI allocated

    toluene                      R           ADI not specified7,10

    1,1,1-trichloroethane        O           No ADI allocated

    Carrier solvents

    diethyl tartrate            NT           No ADI allocated

    1,2-propylene glycol
    acetate                      O           0-2511

    triethyl citrate             S           0-102

    triglycerides (synthetic)    O           No ADI allocated

    Miscellaneous food additives

    calcium ascorbate            O           ADI not specified7,10,12

    polydextroses              R13           0-7014

    polyvidone (poly(vinyl
    pyrrolidone; PVP)            S           0-1

    sodium sesquicarbonate       N           ADI not specified7,10,15

                             Specifications only

    Extraction solvents                        Specifications1
                                                                        

    butane                                            O

    butan-1-ol                                        R

    butan-2-ol                                        O

    cyclohexane                                       R

                             Specifications only

    Extraction solvents                        Specifications1
                                                                        

    1,1-dichloroethane                         O

    diethylene glycol monoethyl ether          R

    diisopropyl ether                          O

    ethylmethyl ketone                         R

    furfural                                   S

    isopropyl acetate                          NT

    tetrachloroethylene                        O

    1,1,2-trichlorotrifluoroethane             NT

    Notes

    1.   N, new specifications prepared; O, specifications not prepared;
         R, existing specifications revised; S, specifications exist,
         revision not considered; T, the existing, new or revised
         specifications are tentative and comments are invited.

    2.   Temporary acceptance.

    3.   Group ADI for riboflavin and riboflavin-5'-phosphate expressed as
         riboflavin.

    4.   On the available evidence, this substance should not be used as a
         food additive.

    5.   Hydrogen cyanide and its salts should not be used as such as food
         additives.

    6.   Group ADI for other glutamate, calculated and expressed as
         glutamic acid.

    7.   The statement "ADI not specified" means that, on the basis of the
         available data (chemical, biochemical, toxicological, and other),
         the total daily intake of the substance, arising from its use at
         the levels necessary to achieve the desired effect and from its
         acceptable background in food, does not, in the opinion of the
         Committee, represent a hazard to health. For this reason, and for
         the reasons stated in the individual evaluations, the
         establishment of an acceptable daily intake (ADI) is not deemed
         necessary.

    8.   Group ADI for pectins and amidated pectins, singly or in
         combination.

    9.   This solvent should not be used in food processing.

    10.  Residues of toluene occurring in foods when this solvent is used
         in accordance with good manufacturing practice would not pose any
         toxicological problems.

    11.  Group ADI for propylene glycol esters of fatty acids calculated
         and expressed as propylene glycol.

    12.  Group ADI. The Committee concluded that the ADI for ascorbic acid
         and its potassium and sodium salts should be changed from
         0-15 mg/kg of body weight to "not specified", and that the
         calcium salt should be included in this ADI.

    13.  The specifications were revised to include a limit for
         5-hydroxymethylfurfural of 0.05%.

    14.  The ADI is for polydextrose A and polydextrose N, singly or in
         combination.

    15.  Group ADI for other carbonates and bicarbonates established in
         the ninth report of the Committee.

    16.  An ADI for diketopiperazine - an impurity found in aspartame was
         established at 0-7.5 mg/kg bw.

    CONTENTS

    THE MONOGRAPHS

    Acesulfame Potassium

    Aspartame*

    beta-Asarone

    Brilliant BLACK PN

    Calcium ascorbate

    Carob (locust) bean gum

    Cinnamyl anthranilate

    Carmines (formerly Cochineal, Carmine and Carminic acid)

    Coumarin

    Eugenyl methyl ether

    Fast Green FCF

    Isomaltitol

    Light petroleum

    Maltol

    2-Nitropropane

    Pectins and Amidated Pectins

    Polydextroses

    Propan-1-ol (n-Propanol)

    Red 2G

    Riboflavin-5'-phosphate

    Safrole

    Tara gum

    Toluene

    Thujone

    1,1,1-Trichloroethane

    ANNEX

              

    *    Addendum.
    




























    See Also:
       Toxicological Abbreviations